|Montante, Steven -|
|Bopp, Alvin - COLLABORATOR, SRRC|
|Bertoniere, Noelie -|
|Yager, Dorne - WOUND HEALING INSTITUTE|
|Cohen, I. Kelman - WOUND HEALING INSTITUTE|
|Diegelmann, Robert -|
Submitted to: Journal of Wound Repair and Regeneration
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 15, 2000
Publication Date: January 1, 2001
Citation: Edwards, J.V., Montante, S., Bopp, A., Bertoniere, N., Yager, D., Cohen, I., Diegelmann, R.F. 2001. Modified Cotton Gauze Dressings that Selectively Absorb Neutrophil Elastase Activity in Solution. Journal of Wound Repair and Regeneration. 9(1):50-58. Interpretive Summary: Chronic wounds are a major worldwide health problem. This research is directed at strengthening the role of cotton-based textiles in the growing market of high tech wound dressings. This paper demonstrates an important technology for development of value-added cotton-based wound dressings. An improvement on cotton gauze to accelerate healing in patients with bedsores and ulcers is the ultimate goal of this work. The paper shows how cotton gauze can be modified to reduce the activity of a destructive enzyme found to keep chronic wounds from healing. The destructive enzyme is human neutrophil elastase. High levels of elastase in the non-healing wound break down the recruitment of new tissue necessary for healing to take place. The advantage of this work suggests that novel gauze modified with both anionic and aldehydic modifications may in the future be preferable over standard gauze widely used in hospitals and nursing homes at present. This preference is based on the mechanism of the molecular modifications, which promote uptake of elastase activity, and decreases the high levels of activity found to be destructive in the non-healing wound. The addition of intelligent cotton-based wound dressings to the market would boost cottons share in the rapidly growing field of high tech wound care, and aid both the consumer and the cotton farmer by providing an economic value-added product.
Technical Abstract: The lowering of high protease activity in the chronic wound has been considered a potentially important therapeutic route to accelerated healing with active chronic wound dressings. Dialdehyde gauze was designed and prepared based on a molecular mechanism for serine protease sequestration and a one-step aqueous textile finishing process. Cotton gauze containing 20% dialdehyde cellulose was found to lower elastase activity eight-fold in chronic wound fluid compared with untreated gauze. In a similar manner up to 70% of proteinase 3 activity was removed from solution, and cathepsin G activity was lowered three-fold. Collagenase activity was slightly lowered owing to a different mechanism of action of the dialdehyde gauze for collagenase uptake. Separate chromatographic columns were prepared with dialdehyde, carboxymethylated, and standard cotton and equilibrated to the physiological pH, temperature, and ionic strength of the wound environment. As a model to assessment of the effect of competitive binding of a wound protein with elastase for the dialdehyde cotton, elastase was eluted on albumin bound cotton columns and enzyme binding to the cotton determined by protein adsorption and enzyme activity. The dialdehyde cotton column was found to bind elastase more effectively in the presence of albumin than the carboxymethylated, and untreated cotton. This approach revealed that albumin interacts with elastase to accelerate the rate of elastase activity. The elastase-lowering activity of the dialdehyde cotton was effective with wound dressing incubations for one, six, and twenty-four hours. The in-situ monitoring of elastase activity in the presence of dialdehyde cotton gauze was determined by assessing the kinetics of substrate hydrolysis in a two-phase system. The in-situ determination of an elastase-lowering effect with the dialdehyde gauze demonstrates that the enzymes is irreversibly bound and is inhibited on the dialdehyde cotton-wound dressing fiber. The protease lowering and inhibitory effect of dialdehyde cotton demonstrates its potential use in neutralizing the destructively high levels of proteases found in chronic wounds with rationally designed wound dressings.